Despite nearly thirty years of research, the in vivo function of mouse submandibular gland nerve growth factor (NGF) remains obscure. One of the reasons for this may be the fact that the naturally-occurring, naturally secreted (in saliva) form of the protein has not been studied before. Recent studies from this laboratory have shown: 1) that extraordinarily large amounts of NGF are secreted in saliva; 2) that the submandibular gland is not an endocrine organ for secretion of NGF; and 3) that NGF, as it is secreted in saliva and as it is present in the gland, is a strikingly different macromolecule from the NGF which has been studied so far. We propose to purify the naturally-occurring form of NGF, to determine its subunit structure, and to compare it chemically with presently known forms of the factor. In light of the very high NGF levels in saliva, possible biological effects of the protein will be looked for in the alimentary tract. No effect of NGF upon non-neuronal components has ever been observed - perhaps because only a fragment of the naturally-secreted form of the molecule has been studied so far. Using a variety of cell types in culture, metabolic effects of this newly-recognized NGF will be studied to see if the action of the factor is in fact confined to the nervous system.